Freeze-fracture techniques will be applied to normal and diseased human intestinal mucosa to study distribution of integral membrane protein particles on the apical plasma membrane and to examine the structure of junctional complexes. Freeze-fracture techniques will also be applied to animal models in which normal function has been perturbed. Substances that alter mucosal permeability, such as bile acids will be infused and the structure of the junctional complexes as revealed by freeze-fracture will be correlated with transmission electron microscopy using visible markers for permeability such as lanthanum and horseradish peroxidase. Tissue resistance factors in peptic ulcer disease will be studied. Specifically, the influence of prostaglandin derivatives that show evidence of cytoprotectivity but do not inhibit gastric secretion on glycoprotein synthesis and secretion will be studied using radioautographic and biochemical methods. The influence of hormonal factors and sulfhydryl-containing chemicals on prostaglandin-induced gastric cytoprotection will be investigated. The factors which influence susceptibility of suckling mice to the rotavirus which causes epizootic diarrhea of infant mice will be examined.